Tumor engineering is defined as the construction of three-dimensional (3D)
tumors in vitro with tissue engineering approaches. The present 3D scaffolds for
tumor engineering have several limitations in terms of structure and function. To get an ideal 3D scaffold for
tumor culture, A549 human pulmonary
adenocarcinoma cells were implanted into immunodeficient mice to establish xenotransplatation models.
Tumors were retrieved at 30-day implantation and sliced into sheets. They were subsequently decellularized by four procedures. Two decellularization methods, Tris-
Trypsin-Triton multi-step treatment and
sodium dodecyl sulfate (SDS) treatment, achieved complete cellular removal and thus were chosen for evaluation of histological and biochemical properties. Native
tumor tissues were used as controls. Human
breast cancer MCF-7 cells were cultured onto the two 3D scaffolds for further cell growth and
growth factor secretion investigations, with the two-dimensional (2D) culture and cells cultured onto the
Matrigel scaffolds used as controls. Results showed that Tris-
Trypsin-Triton multi-step treated
tumor sheets had well-preserved extracellular matrix structures and components. Their porosity was increased but elastic modulus was decreased compared with the native
tumor samples. They supported MCF-7 cell repopulation and proliferation, as well as expression of
growth factors. When cultured within the Tris-
Trypsin-Triton treated scaffold, A549 cells and human colorectal
adenocarcinoma cells (SW-480) had similar behaviors to MCF-7 cells, but human
esophageal squamous cell carcinoma cells (KYSE-510) had a relatively slow cell repopulation rate. This study provides evidence that Tris-
Trypsin-Triton treated acellular
tumor extracellular matrices are promising 3D scaffolds with ideal spatial arrangement, biomechanical properties and biocompatibility for improved modeling of 3D tumor microenvironments.